MD Anderson DNA study reveals new insights in colon cáncer, may help personalize treatment options and Scientists untangle Barr body of

inactive X chromosome: Highly elaborate chromosome structure

Tatiana Gómez González Medicine third semester

UPB

To have now more information to prevent cáncer, have more specific information about pre cancerous lessions, mutations or structure of the tumor and in that way, give the patient the best treatment to prevent or end the desease, improving their health and lifestyle.

With this study we can now have more tools to understand how the DNA works and it’s structure in the genome. Also to investigate about the active parts of the Barr Body to see if maybe they are responsable of some functions or deseases that we could turn off in females to protect them..

MD Anderson DNA study reveals new insights in colon cáncer, may help personalize treatment options and Scientists untangle Barr body of inactive X chromosome: Highly elaborate chromosome structure

Tatiana Gomez Gonzalez Molecular Biology Third semester

Teacher: Lina Martinez

August 4th 2016

Medical utility References

• Journal reference: Kegel Magalena. MD Anderson DNA Study Reveals New Insights in Colon Cancer, May Help Personalize Treatment Options. Bionews Texas. July 25th 2015. https://bionews-tx.com/news/2016/07/25/md-anderson-colon-cancer-dna-mismatch-repair-deficiency-insights-personalize-treatment/.

• Journal reference: Luca Giorgetti, Bryan R. Lajoie, Ava C. Carter, Mikael Attia, Ye Zhan, Jin Xu, Chong Jian Chen, Noam Kaplan, Howard Y. Chang, Edith Heard, Job Dekker. Structural organization of the inactive X chromosome in the mouse. University of Massachusetts Medical School. Nature, 2016; DOI: 10.1038/nature18589. https://www.sciencedaily.com/releases/2016/07/160721143503.htm

• Paul L. Modrich. DNA Mismatch Repair and Genetic Stability. Howard Hughes Medical Institute. http://www.hhmi.org/research/dna-mismatch-repair-and-genetic-stability

• Wikipedia. Barr Body. July 16th 2016. https://en.wikipedia.org/wiki/Barr_body

• The Cell Cycle & Mitosis Tutorial. The biology project, cell biology. Department o biochemistry and molecular biophysics. University of Arizona. August 2004. http://www.biology.arizona.edu/cell_bio/tutorials/cell_cycle/cells2.html

Reserchers of the University of Texas MDAnderson Cancer Center found some genes that were responsable of allowing the formation of mutations in genes linked to rectal cáncer, and that were previously not taked into account. This is ¨the DNA mismatch repair system¨.They found that DNA mismatch repair deficiency was impact of prognosis of rectal cáncer and that this can help physicians in the diagnoses and choosing tratments for their patients.they explain that after chromosemes are duplicated , there are occasional errors that the DNA mismatch rapair, but when it is dysfunctional, there are more posibilities of developing cáncer.Four genes are in charge of control the system, but two genes are rsponsable of it{s breakdown (MLH1 and MSH2), but in a study lead by Dr. You, there were two other genes related with this condition (MSH2 and also MSH6)With this discoverment Dr. You talked about the power of precisión medicine and that with this new genetic understanding of DNA mismatch deficiency we can now have more specific information of owr patients conditions, choose the best treatment depending in their personal desease and detect pre cancerous lesions in order to remore them early.

Comment: This study is important because now we can treate better cáncer patients and also the ones that still dont have it preventing it, prolonging lfe and human health.

Scientists at Umass Medical School, taked a detailed look of the Barr Body and developed a model system in order to understand its structure and gene expression.

Te Barr Body has been thought to be a extrange structure but the new study reveals that it is highly organized with condensed inactive DNA and with small domains of active DNA that have an important role in gene expression, their presence was sorprising. They saw it under the microscope and it looked diferent to other chomosomes,the shape it takes when the genome folds and loops back itself has influence on which cells are turne off and that also the chromosome has a macrosatelite repeat and that this structure posibly has a big impact on it{s shape and function.They also said that genes that are being expresed reside on topological associating domains (TADs) and that they are in charge of gene expression.

Comment: thus study is realy interesting because now, scientists will learn more about the genome of living things, find new structures and compare the differecnces between a normal chromosome and a Barr Body.

This brouchure will show you information and discoveries of two important studies that were published on july of this year related with molecular biology, as they talk abut gentics, chromosomes, genes and some proteins that are related with some deseaces. All this was realized with some techniques that will help the medical field in order to prevent patologies or understand better our genome for giving the best treatment to our patients.

Introduction MD Anderson DNA study

revealsnew insights in colon cáncer, may help personalize

treatment options

Scientists untangle Barr body of inactive X chromosome:

Highly elaborate chromosome structure

IntroductionThe introdiction has the purpose of capture the reader’s attention, more specfically people that study biology or medicine and also pharmacology in order to learn about new discoveries, tratments for patients, solutions or maybe to inspire an idea for a new invention or tecnique that involves the genetics área.

The first study talks about the déficit in some genes that are in charge in the nuclear cycle of preventig the mutation of bad cells, and how they are not in 100% effective or working, then is why o the reasonswhy cáncer appear.

The second study is about the analysis and determination of the figure and structure of the innactive x chromosome, the Barr Body, located in females, but surprisingliy, they found that some of its domains had active genes that maybe are in charge of something in women.

This brouchure will show you information and discoveries of two important studies that were published on july of this year related with molecular biology, as they talk abut gentics, chromosomes, genes and some proteins that are related with some deseaces. All this was realized with some techniques and that will help the medical field in order to prevent patologies or understand better our genome for giving the best treatment to our patients.

Introduction

The DNA mismatch repair system:DNA mismatch repair is a system for recognizing and repairing erroneous insertion, deletion, and mis-incorporation of bases that can arise during DNA replication and recombination, as well as repairing some forms of DNA damage.Mismatch repair is strand-specific. During DNA synthesis the newly synthesised (daughter) strand will commonly include errors. In order to begin repair, the mismatch repair machinery distinguishes the newly synthesised strand from the template (parental).Any mutational event that disrupts the superhelical structure of DNA carries with it the potential to compromise the genetic stability of a cell. BUT IN THE STUDY…

Reserchers of the University of Texas MDAnderson Cancer Center found some genes that were responsable of allowing the formation of mutations in genes linked to rectal cáncer, and that were previously not taked into account. This is ¨the DNA mismatch repair system¨.They found that DNA mismatch repair deficiency was impact of prognosis of rectal cáncer and that this can elp physicians in the diagnoses and choosing tratments for their patients.they explain that after chromosemes are duplicated , there are occasional errors that the DNA mismatch rapair, but when it is dysfunctional, there are more posibilities of developing cáncer.Four genes are in charge of control the system, but two genes are rsponsable of it{s breakdown (MLH1 and MSH2), but in a study lead by Dr. You, there were two other genes related with this condition (MSH2 and also MSH6)With this discoverment Dr. You talked about the power of precisión medicine and that with this new genetic understanding of DNA mismatch deficiency we can now have more specific information of owr patients conditions, choose the best treatmentdepending in their personal desease and detect pre cancerous lesions in order to remore them early.

Comment: This study is important because now we can treate better cáncer patients and also the ones that still dont have it preventing it, prolonging lfe and human health.

MD Anderson DNA study revealsnew insights in colon cáncer, may help personalize

treatment options

DNA mismatch repair system is DEFICIENT

CANCER

Cell CycleWhen cells divide, and chromosomes are copied and duplicated (phase S) occasional errors during the copy processlead to mutations in the new chromosomes, here is where the DNAmismatch system works making sure the errors are corracted.In cáncer this process is alterated and the bad chomosomes get formed and continue the cell cycle till reaching the phase M in which cells suffer mitosis producing new daughters with bad DNA.

Mutation Bad cells

Genes that are involved in the problemFour genes are known to control the system (MSH6, MSH2, MLH1 AND PMS2) A recent study suggested that two of them are involvedin the breakdown of the system. (MLH1 and MSH2)Dr. You and her team studied 62 patients with colorectal cáncer and discovered other genes that were involved in this people. (MSH2 but aldso MSH6) WITH THIS THE STUDY SHOWED THAT ARE DIFFERENT PROFILES OR TYPES OF COLORECTAL TUMORS.

Main aim With this study they prove the power of the precisión medicine and its utility in the diagnosis of cáncer and it´s best treatment.This new way of understanding the factors that determinate a type of cáncer provides inmediate implications for telling patients how well they will do long term, and the gravity of their condition.

Best treatment

POWERFUL

Student observation

Only good news are bring with this study to society, because now, with this discoverment (genes that are involved in DNA mismatch deficiency) we can have more specific informaton about pre cancerous lessions, mutations or structure of a specific tumor, giving patients better and more efective treatments, improving life quality and making them healthier and happier.

Barr BodyIt is though to be the inactive X chromosome in an female somatic cell, inactivated in a proccess called iyonization. The chromosome is silenced by its being packaged in such a way that it has a transcriptionally inactive structure called heterocromatin.The chce of which x cromosome will be inactivated is random, but once it is inactivated it will remain inactive trhougthout the lifetime of the cell and its descendants in the organism.

Scientists at Umass Medical School, taked a detailed look of the Barr Body and developed a model system in order to understand its structure and gene expression.

Te Barr Body has been thought to be a extrange structure but the new study reveals that it is highly organized with condensed inactive DNA and with small domains of active DNA that have an important role in gene expression, their presence was sorprising. They saw it under the microscope and it looked diferent to other chomosomes,the shape it takes when the genome folds and loops back itself has influence on which cells are turne off and that also the chromosome has a macrosatelite repeat and that this structure was posibly has a big impact on it{s shape and function.They also said that genes that are being expresed reside on topological associating domains (TADs) and that they are in charge of gene expression.

Comment: thus study is realy interesting because now, scientists will learn more about the genome of living things, find new structures and compare the differecnces between a normal chromosome and a Barr Body.

Scientists untangle Barr body of inactive X chromosome:

Highly elaborate chromosome structure

Surprising structure of the Barr Body… and new discovermets.

• The DNA folds and loops back on itself so it can fit tight in the nucleous

• Doctors wanted to know more about the pieces of active DNA in the Barr Body so they used suite of chromosome conformation capture technologies that consist on biochemical techniques for determinating how DNA segments interact and are linked to one another.

A group of scientists looked the Barr Body under the microscope and they fuond it was very different tan other chromosomes.

They used a range of experimetal aproaches including imaging and genomic methods that described something realy different:

It looked like a condensed undefines inactive blob

A hightly organized and elaborate stucture rich in feaures that may silence or actívate genes all along the chromosome!

The shape it takes has influence on which genes in a cell are turnes on or off

They constructed a detailed view of the shape and architecture or

th inactive x chromosome

They build a three dimensional model o the inactive x inside the Barr Body.

The truth about the Barr Body• It wasn´t a single dense mass of

DNA.• It was composed of TWO

SEPARATELY PACKED LOBES SEPARATED BY A HIGHLY REPETITIVE SEGMENT OF DNA:

• Found in only few places in the genome.

• When the scientists tried to remove the macrosatellite from the Barr Body they found that the BI LOBED STRUCTURE DISAPPEARED.

• There are also some genes inside the lobes that are being EXPRESED. They are inside some domains:

A macrosatellite repeat

Responsable of packing and organizing DNA inside the x chromosome

This element has a global impact on shape and function in a chromosome

TADs

Organize the genome in a way that transcription is repress

They make a role in organizing gene expression and in that way INACTIVATING THE X CHROMOSOME LOBES

Conclutions • They conclude that in order for a

gene to be expressed inside the inactive Barr Body, it has to be locaed in the TADs.

• TADs play a kind of protective role allowing genes to be accesible for expression even when they are located inside the condensed and inactive chromosome.

• The Barr Body is a powerful model sysem for studying the spatial organization of the genome and gene expression that will help us learn more about the amazing things that we are made of.

Student observation Studying and discovering the structure

of the Barr Body and the characteristics it has, we can now have more tools and elements to understand it´s function and how the DNA works and is organized in this chromosome.

Some specific parts of it are ACTIVE, which means that if we continue studying and exploring these regions maybe we could find genes in charge of expressing especific charactericstics that we colud turn off or on in order to impruve women´s health.

Medical utilityThis new is really important and shocking in the society nowadays, bacause cáncer is one of the most common patologies of which people is dying, and how they discovered some of the factors that cause colorectal cáncer, that mean we can go futher in investigations till we find the cure or a more effective treatment, saving lifes and improving on people´s health.

Medical utilityThe best thing is that this study not only function to have better treatments but to prevent this patgy too, detecting it earlier and avoiding this situation.

Medical utilityWith this new, we can conclude that our body has no ending and that we can now undestand better and learn new things about the Barr Body, it´s structure and function.

Also that we can investigate and continue analyzing this misterious chromosome, and that maybe it has secrets that can benefit not only medicine, but mostly importatant our patients, improving their heatlh and lifestyly by turning on or off parts of the Barr Body that can influence in their lives.

Medical utility

Also that we can investigate and continue analyzing this misterious chromosome, and that maybe it has secrets that an benefit not only medicine, but mostly important our patients, impruving their health and lifestyle by turning on or off specific parts of the Barr Body that can influence in their health state.

References• Journal reference: Kegel Magalena. MD Anderson DNA Study Reveals New Insights in

Colon Cancer, May Help Personalize Treatment Options. Bionews Texas. July 25th 2015. https://bionews-tx.com/news/2016/07/25/md-anderson-colon-cancer-dna-mismatch-repair-deficiency-insights-personalize-treatment/.

• Paul L. Modrich. DNA Mismatch Repair and Genetic Stability. Howard Hughes Medical Institute. http://www.hhmi.org/research/dna-mismatch-repair-and-genetic-stability

• The Cell Cycle & Mitosis Tutorial. The biology project, cell biology. Department o biochemistry and molecular biophysics. University of Arizona. August 2004. http://www.biology.arizona.edu/cell_bio/tutorials/cell_cycle/cells2.html

• Journal reference: Luca Giorgetti, Bryan R. Lajoie, Ava C. Carter, Mikael Attia, Ye Zhan, Jin Xu, Chong Jian Chen, Noam Kaplan, Howard Y. Chang, Edith Heard, Job Dekker. Structural organization of the inactive X chromosome in the mouse. University of Massachusetts Medical School. Nature, 2016; DOI: 10.1038/nature18589. https://www.sciencedaily.com/releases/2016/07/160721143503.htm

• Wikipedia. Barr Body. July 16th 2016. https://en.wikipedia.org/wiki/Barr_body